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R. Hodge
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MA08 - Treatment Monitoring in Advanced NSCLC (ID 386)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:R. Perez-Soler, T. Reungwetwattana
- Coordinates: 12/06/2016, 11:00 - 12:30, Lehar 3-4
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MA08.03 - Osimertinib vs Platinum-Pemetrexed for T790M-Mutation Positive Advanced NSCLC (AURA3): Plasma ctDNA Analysis (ID 4733)
11:00 - 12:30 | Author(s): R. Hodge
- Abstract
- Presentation
Background:
AURA3 (NCT02151981) is a Phase III, open-label, randomised study assessing the efficacy and safety of osimertinib, a T790M directed EGFR-TKI, vs platinum-based doublet chemotherapy in patients with EGFR T790M-positive advanced NSCLC, whose tumours progressed on previous EGFR-TKI therapy. Concordance between plasma and tissue testing, and efficacy outcomes by baseline plasma T790M status, were evaluated.
Methods:
Eligible patients were randomised 2:1 to osimertinib 80 mg orally once daily or platinum-pemetrexed (pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 or carboplatin AUC5) every three weeks for up to six cycles. Patients were tumour tissue T790M-positive (by cobas[®] EGFR Mutation Test v2) from a biopsy after disease progression prior to study entry. Blood samples were taken at baseline for retrospective analysis of T790M mutation status by plasma ctDNA using the cobas[®] EGFR Mutation Test v2.
Results:
Concordance data are reported in the table. Within the intent-to-treat (ITT) population (n=419), patients plasma T790M-positive and randomised to treatment (n=172) had markedly improved progression-free survival (PFS) by investigator assessment (IA) with osimertinib vs platinum-pemetrexed: hazard ratio 0.42 (95% CI: 0.29, 0.61); median 8.2 vs 4.2 months. Objective response rate (ORR) by IA was also distinctly improved with osimertinib vs platinum-pemetrexed: 77% vs 39% (odds ratio 4.96 [95% CI: 2.49, 10.15]; p<0.001). This is consistent with the ITT population: PFS hazard ratio 0.30 (95% CI: 0.23, 0.41); p<0.001 (median 10.1 vs 4.4 months); ORR 71% vs 31% (odds ratio 5.39 [95% CI: 3.47, 8.48]; p<0.001). Figure 1
Conclusion:
In plasma T790M-positive patients the clinical benefit of osimertinib was superior to platinum-pemetrexed, consistent with the ITT T790M-positive population selected by tumour tissue test. PFS with osimertinib was similar regardless of selection by tissue or plasma T790M-positive status. Based on these, and AURA Phase II data, routine biopsy testing is recommended for patients with a plasma T790M-negative test where feasible.
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MA16 - Novel Strategies in Targeted Therapy (ID 407)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
- Moderators:G. Purkalne, J. Von Pawel
- Coordinates: 12/07/2016, 14:20 - 15:50, Strauss 2
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MA16.11 - CNS Response to Osimertinib in Patients with T790M-Positive Advanced NSCLC: Pooled Data from Two Phase II Trials (ID 4920)
14:20 - 15:50 | Author(s): R. Hodge
- Abstract
- Presentation
Background:
Brain metastases develop in 25–40% of patients with NSCLC. Osimertinib is an oral, potent, irreversible EGFR-TKI, selective for both sensitising (EGFRm) and T790M resistance mutations. Preclinical and early clinical evidence support central nervous system (CNS) penetration and activity of osimertinib. Two Phase II studies (AURA extension [NCT01802632] and AURA2 [NCT02094261]) evaluating the efficacy and safety of osimertinib are ongoing. We present a pre planned subgroup analysis assessing pooled CNS response from these two studies; data cut-off (DCO) was 1 November 2015. An earlier pooled analysis from these two studies (1 May 2015 DCO) showed the objective response rate (ORR) in patients with CNS metastases was consistent with ORR in the overall patient population.
Methods:
Patients with advanced NSCLC who progressed following prior EGFR-TKI therapy with centrally-confirmed T790M positive status (cobas® EGFR Mutation Test) received osimertinib 80 mg once daily (n=411). Patients with stable, asymptomatic CNS metastases were eligible for enrolment. CNS efficacy was assessed in an evaluable for CNS response analysis set, which included patients with at least one measurable CNS lesion on baseline brain scan (RECIST v1.1) by blinded independent central neuroradiology review (BICR). Effect of prior radiotherapy on CNS response was assessed.
Results:
As of 1 November 2015, 50/192 patients with baseline brain scans had at least one measurable CNS lesion identified by BICR. Baseline demographics were broadly consistent with the overall patient population. Confirmed CNS ORR was 54% (27/50; 95% CI: 39%, 68%), with 12% complete CNS response (6/50 patients). The median CNS duration of response (22% maturity) was not reached (95% CI: not calculable [NC], NC). The estimated percentage of patients remaining in response at 9 months was 75% (95% CI: 53, 88). CNS disease control rate (DCR) was 92% (46/50; 95% CI: 81%, 98%). Median time to first response was 5.7 weeks (range: 5.6–6.6). Median best percentage change from baseline in CNS target lesion size was 53% (range: -100% – +80%). Median follow up for CNS progression-free survival (PFS) was 11 months; the median CNS PFS was not reached (95% CI: 7, NC). At 12 months, 56% (95% CI: 40%, 70%) of patients were estimated to remain on study, alive and CNS progression-free. CNS response was observed regardless of prior radiotherapy to the brain.
Conclusion:
Osimertinib demonstrates durable efficacy in patients with T790M NSCLC and measurable CNS metastases, with a CNS response rate of 54% and a DCR of 92%.
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